This Program Project combines the disciplines of engineering mechanics, physiology, pharmacology, anesthesiology, medicine and critical care to study the mechanical behavior of the respiratory system in health and disease. Combined experimental and modeling approaches address the mechanics of the chest wall including the interaction of thorax and abdomen, the mechanics of the diaphragm, the mechanical properties of the lung parenchyma, and the determinants of regional ventilation. Unique new methodology is employed which determines diaphragmatic shape, displacement and regional contraction. The respiratory actions of muscles and their integration in the process of respiration are examined. These studies will contribute to the development of specific and objective tests for diaphragmatic fatigue in man which can be used to evaluate less invasive ways of assessing the balance between mechanical load and endurance of the respiratory muscles in patients with respiratory failure. They should also lead to more rational care of such patients. In vitro studies examine the control of airway and pulmonary vascular smooth muscle with particular emphasis on the modulating influence of the epithelium and on interactions between the two components. These studies will be extended to animal models of reactive airway disease. Other related studies elucidate the mechanisms of changes in airway resistance produced by anesthetic agents and other drugs used in surgery. These studies are not only of great clinical importance but may explain apparently conflicting results in the literature on airway reactivity in which different anesthetic regimens have been employed.